FDA Grants Priority Review to Belantamab Mafodotin for Heavily-treated Multiple Myeloma

The U.S. Food and Drug Administration (FDA) has granted priority review status to GlaxoSmithKline‘s application seeking the approval of belantamab mafodotin for the treatment of heavily treated multiple myeloma patients, the company announced in a press release.

The biologics license application (BLA) is specifically asking for belantamab’s approval for people with relapsed or refractory disease who received prior treatment with an immunomodulatory agent, a proteasome inhibitor, and a CD38-targeting antibody.

FDA priority review means that a final decision is expected within six months, rather than the 10 months normally taken under standard review.

Belantamab mafodotin — granted a breakthrough therapy designation by the FDA in 2017 — is an antibody-drug conjugate that targets B-cell maturation antigen (BCMA), a cell surface receptor present on virtually all multiple myeloma cells. BCMA is absent from normal B-cells, making it an ideal target for therapy.

The therapy is an antibody-drug conjugate, composed of an anti-BCMA monoclonal antibody bound to the toxic molecule auristatin F. Once belantamab binds to BCMA, the cancer-killing molecule is released into the cell and causes cell death.

If approved, belantamab mafodotin will become the first available anti-BCMA treatment.

The BLA was based on positive data from the open-label DREAMM-2 Phase 2 clinical trial (NCT03525678), designed to test belantamab mafodotin as a fourth-line or later therapy.

Participants had received at least three prior lines of therapy and had failed to respond to an immunomodulatory agent such as Revlimid (lenalidomide), a proteasome inhibitor such as Velcade (bortezomib), and an anti-CD38 antibody such as Darzalex (daratumumab).

Enrolled patients, a total of 196, were randomized to one of two belantamab mafodotin doses — 2.5 mg/kg (97 patients) or 3.4 mg/kg (99 patients) — given once every three weeks. Patients had received a median of seven prior lines of therapy, with some having been treated up to 21 times.

The trial’s main goal was to determine the proportion of patients responding to treatment. Secondary measures included duration of response, time to disease progression or death, overall survival, safety, and a number of laboratory assessments.

Results published in December showed that after a median follow-up of 6.3 months for the 2.5 mg/kg dose, 31% of patients had achieved an overall clinical response, including 19% very good partial responses or better. For those on the higher dose, 34% responded to treatment after a median follow-up of 6.9 months, and 20% were very good partial responses or better.

Three patients in each dose group achieved complete responses.

The median time patients lived without disease progression was 2.9 months for those on the lowest dose, and reached 4.9 months for patients receiving the highest dose. However, more patients on the highest dose had to reduce their treatment dose during the trial, and more of these patients died due to a serious adverse event (7% versus 3% for the lowest dose).

Based on these results, GlaxoSmithKline announced it would request the approval of the 2.5 mg/kg dose.

The company is conducting additional studies to test the therapy in combination with standard and new treatments in myeloma patients who failed one or two prior lines of therapy as part of the DREAMM clinical trial program.